Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

Cathepsin X/Z/P is cysteine cathepsin with unique carboxypeptidase activity. Its expression is associated with cancer and neurodegenerative diseases, although its roles during normal physiology are still poorly understood. Advances in our understanding of its function have been hindered by a lack of available tools that can specifically measure the proteolytic activity of cathepsin X. We present a series of activity-based probes that incorporate a sulfoxonium ylide warhead, which exhibit improved specificity for cathepsin X compared to previously reported probes. We apply these probes to detect cathepsin X activity in cell and tissue lysates, in live cells and in vivo, and to localize active cathepsin X in mouse tissues by microscopy. Finally, we utilize an improved method to generate chloromethylketones, necessary intermediates for synthesis of acyloxymethylketones probes, by way of sulfoxonium ylide intermediates. In conclusion, the probes presented in this study will be valuable for investigating cathepsin X pathophysiology.


Simon J Mountford, Bethany M Anderson, Bangyan Xu, Elean S V Tay, Monika Szabo, My-Linh Hoang, Jiayin Diao, Luigi Aurelio, Rhiannon I Campden, Erik Lindström, Erica K Sloan, Robin M Yates, Nigel W Bunnett, Philip E Thompson, Laura E Edgington-Mitchell. Application of a Sulfoxonium Ylide Electrophile to Generate Cathepsin X-Selective Activity-Based Probes. ACS chemical biology. 2020 Mar 20;15(3):718-727

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 32022538

View Full Text